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A a Y.TIC FILE CO Y NATURAL HISTORY OF HTLV III INFECTION IN USAF PERSONNEL: CLINICAL EVALUATION, LABORATORY EVALUATION, ASSESSMENT OF IN VIVO AND IN VITRO IMMUNOLOGIC STATUS, AND DATA STORAGE Lt ANNUAL REPORT q ". BY IR. NEAL BOSWELL ROBERT A. ZAJAC December 1988 Supported by U.S. ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND Fort Detrick, Frederick, Maryland 21701-5012 Contract No. DAMD17-86MM6508 WILFORD HALL USAF MEDICAL CENTER O T IC LACKLAND AFB, TX 78236-5300 S LECT 0 1JUL B IS19 Approved for public release; distribution unlimited. The findings in this report are not to be construed as an official Department of the Army position unless so designated by other authorized documents. *0 0o" 18 , 43

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Page 1: REPORT DOCUMENTATION PAGE · 2011-05-15 · normal CD4a counts, and finally that clinical AIDS dementia complex affects less than 10% of the USAF HIV-infected population in late-stage

A a Y.TIC FILE CO YNATURAL HISTORY OF HTLV III INFECTION IN USAF PERSONNEL:

CLINICAL EVALUATION, LABORATORY EVALUATION,ASSESSMENT OF IN VIVO AND IN VITRO IMMUNOLOGIC STATUS, AND DATA STORAGE

LtANNUAL REPORT

q ". BY

IR. NEAL BOSWELL

ROBERT A. ZAJAC

December 1988

Supported by

U.S. ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMANDFort Detrick, Frederick, Maryland 21701-5012

Contract No. DAMD17-86MM6508

WILFORD HALL USAF MEDICAL CENTER O T ICLACKLAND AFB, TX 78236-5300 S LECT 0

1JULB IS19

Approved for public release; distribution unlimited.

The findings in this report are not to be construed as an official Departmentof the Army position unless so designated by other authorized documents.

*0 0o" 18 , 43

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SECURITY CLASSIFICATION OF THIS PAGEForm Approved

REPORT DOCUMENTATION PAGE OMB No. 0704-0188

Ia. REPORT SECURITY CLASSIFICATION lb RESTRICTIVE MARKINGS

Unclassified2a. SECURITY CLASSIFICATION AUTHORITY 3. DISTRIBUTION /AVAILABILITY OF REPORT

Approved for public release;2b. DECLASSIFICATION / DOWNGRADING SCHEDULE distribution unlimited

4. PERFORMING ORGANIZATION REPORT NUMBER(S) 5. MONITORING ORGANIZATION REPORT NUMBER(S)

6a. NAME OF PERFORMING ORGANIZATION 6b. OFFICE SYMBOL 7a. NAME OF MONITORING ORGANIZATIONWilford Hall USAF Medical (If applicable)

Center SGHMM

6c. ADDRESS (City, State, and ZIP Code) 7b. ADDRESS (City, State, and ZIP Code)

Lackland AFB, TX 78236-5300

8a. NAME OF FUNDING/SPONSORING [Bb. OFFICE SYMBOL 9. PROCUREMENT INSTRUMENT IDENTIFICATION NUMBERORGANIZATION[ (If applicable)

Research Development Command DAMDI7-86MM6508

8c. ADDRESS (City, State, and ZIP Code) 10. SOURCE OF FUNDING NUMBERSPROGRAM PROJECT TASK WORK UNIT

Fort Detrick ELEMENT NO. NO. 3M2- NO. ACCESSION NO.Frederick, Maryland 21701-5012 63105A 63105DH29IAA 024

11. TITLE (Include Security Classification)Natural History of HTLV III Infection in USAF Personnel: Clinical Evaluation, Laboratory

Evaluation, Assessment of In Vivo and In Vitro Immunologic Status, and Data Storage

12. PERSONAL AUTHOR(S)

13a. TYPE OF REPORT 13b. TIME COVERED 114. DATE OF REPORT (Year, Month, Day) IS. PAGE COUNTAnnual I FROM 87/9/15 TO8/L9L141 1988 Decembor 1

15. SUPPLEMENTARY NOTATION

17. COSATI CODES 18. SUBJECT TERMS (j-;9fwfkte , , , IWLe 3 8ryvnd 4defifby- bkwk-numbhr)

FIELD GROUP SUB-GROUP HTLV III/HIV natural history, HIV disease progression, USAF

06 03 active duty military HIV, HIV neurological disease, RAI,06 13 prognostic markers of disease progression s ory-neural

19. ABSTRA Conttnuo on reverie if necessary and identify by block number)Che Wilford Hall USAF Medical Center HIV Scientific Study Group has

continued our investigation into the Natural History of HIV disease In activeduty USAF personnel and their dependants with intensive immunological

evaluation and staging according to the Walter Reed staging classification.Significant progression over 12 months of observation appears to be

approximately 10%. Studies to determine a marker of disease progression other

than absolute CD4a lymphocyte counts are ongoing.

Our large neurological natural history study has continued on all activeduty HIV-seropositive individuals and they continue to receive full

neurological evaluations as well as CSF analysis. Our data demonstrate that

the CSF immune response is maximal in early-stage HIV disease and more bluntedwith respect to both absolute CSF lymphocyte numbirs and B-cell immunologicresponse when CD4a counts drop below 400 cells/mm . I Ongoing evaluation of

20 DISTRIBUTION /AVAILABILITY OF ABSTRACT 21. ABSTRACT SECURITY CLASSIFICATION0 UNCLASSIFIED/UNLIMITED 01 SAME AS RPT. 0 DTIC USERS Unclassified

22a. NAME OF RESPONSIBLE INDIVIDUAL 22b. TELEPHONE (include Area Code) 22c. OFFICE SYMBOLMary F. Bostian (301) 663-7325 1 SGRD-RMI-S

DD Form 1473, JUN 86 Previous editions are obsolete. SECURITY CLASSIFICATION OF THIS PAGE

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Continued from #18

hearing loss, immunologic function, T-lymphocyte function

Continued from #19

cognitive function of HIV-infected individuals demonstrates that health-relatedanxiety may adversely affect neuropsychological testing when accomplished inassociation with an individual being first told that they were HIVseropositive. Further, differences in cognitive functiIn, however subtle, werenoted in individuals with CD4a counts less than 220/mm compared to those withnormal CD4a counts, and finally that clinical AIDS dementia complex affectsless than 10% of the USAF HIV-infected population in late-stage disease. CSFanti-cardiolipin IgG levels may serve as a potential marker for development ofHIV-related CNS disease. Studies involving nerve conduction demonstrate aprogressive decline in nerve conduction parameters associated with the declinein CD4a counts in HIV-infected individuals. An extensive evaluation of oralhairy leukoplakia demonstrates that OHL is a significant marker for diseaseprogression but the percentages of progression to AIDS from early stage diseasemay be much lower than that previously reported which may reflect the overallearlier stage disease of our patient population.

Icession For

NTIS GRA&I j7

DTIC TAB C1Unannounced 0

Justification

ByDistribution/Availmbility Codes

Avail and/or

Dint Special

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I. Natural History

During the past year, we have continued our investigation into the natural

history of HIV disease in active duty USAF personnel and their Jependants. To

date, approximately 870 HIV positive patients have been entered into the WHMC

databank. Of these approximately 815 have been active duty USAF members, the

remainder are dependants and retirees. Approximately 100 patients have met the

CDC criteria for the diagnosis of AIDS. Approximately 400 USAF patients have

undergone re-evaluation, of these 38% have progressed by the Walter Reed

staging criteria, but when discounting progression of Walter Reed stage 1 to

stage 2 (28%), 10% of these patients have shown significant progression at 1

year re-evaluation. Of note the rate of progression is much higher in patients

who are Walter Reed stage 4 and 5 than in earlier Walter Reed stages. Among

variables studied for correlation with disease progression have been absolute

CD4a helper lymphocyte count, CD4a to CD8 ratio, serum IgG, IgA, IgM, and IgE,

the presence of partial or complete anergy, presence of oral hairy leukoplakia,

as well as standard chemistry profiles and hemograms.

II. T-Lymphocyte Function

In addition, a burgeoning collaboration with investigators at the National

Institutes of Health has included work in the lab of Dr Gene Shearer, Dr Jay

Berzowsky, and Dr Hana Golding. Investigations in these labs have included:

analysis of T-helper cell responses to both mitogens and specific soluble

antigens, analysis of responsiveness of T lymphocyte L-2 production and in

vitro proliferation in response to synthetic HIV peptides using peptides

generated by Dr Berzowsky, analysis of antibody which cross-reacts with HLA-DR

and HIV-1gp41 which may lead to T-lymphocyte depletion and functional

impairment of T-lymphocyte responses.

III. HIV Neurological Disease

In addition, a large neurological natural history study has been conducted

whereby all active duty HIV positive individuals receive a neurological

evaluation by board certified neurologists. In addition, formal audiometric

testing is conducted on all active duty and retired Air Force personnel toassess the impact of HIV on auditory function. Preliminary results reported by

Dr Ann Bell indicate that there is a significant hearing impairment in HIV

positive individuals beyond that which can be attributed to occupational

exposure.The neurological nitro history study has continued on all active duty HIV

seropositive individuals. They continue to receive a complete neurological

evaluation by a board certified neurologist and a lumbar puncture to analyze

CSF parameters including protein, glucose, nucleated cell count, CSF IgG, IgGindex, IgG synthesis rate, oligloconal bands, and in selected cases myelin

basic protein, HIV culture and p-24 antigen detection. Selective patients

receive detailed neuropsychiatric evaluations, including psychiatric

consultation and neuropsychological testing.

Findings thus far in the neurological arm of the study include ourobservation that the incidence of opportunistic infection, progressive

multifocal leukoencephalopathy, and primary CNS lymphoma is parallel to the

experience reported nationally. In our study of CSF in 323 neurologically

asymptomatic HIV-1 infected USAF personnel with at least 2 CSF studies, and a

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minimum of 270 days between analyses, it was found that there are significant(p<.05) increases over time in nucleated cell counts, measures of intrathecalIgG production (especially in immunocompetent patients) and decreased proteinlevels. When CD4a counts drop below 400 cells/mm , cellular responses andimmunologically changes were less impressive. Although weighted towardspatients with higher CD4a counts, these data suggest that the CSF immuneresponse is maximal when the patient is immunocompetent and more blunted withrespect to both absolute CSF lymphocyte numbIrs and B-cell immunologicalresponse when CD4a counts drop below 400 cells/mm .

Evaluation of cognitive function of HIV-infected individuals showedimportant findings in three parallel studies. First, a follow-up study of thepatients published in Archives of Neurology, Feb 1989, revealed that in 50patients who underwent our battery of neuropsychological testing afterapproximately 1 year revealed that not only was there no significant decline inneuropsychological functioning, but in many of the subtests there weresignificant improvements. These data were interpreted as indicating thathealth-related anxiety may adversely impact on neuropsychological testing whenaccomplished in association with an individual being first told that they areHIV seropositive. Another study reviewed the neuropsychological parameterswith respect to both CD4a counts and CSF production of IgG. Consistent withour previous findings, the analysis Indicates3 that patients with abnormalimmune parameters (CD4a counts less than 200/mm , elevated CSF IgG index, orelevated IgG synthesis) had significantly lower scores (but within normalrange) on tests measuring motor speed, verbal memory acquisition and visualmotor speed, and mental tracking. These data emphasize the need fordistinguishing between immunological differences of patients in early and latestages of HIV infection during research assessing cognitive functioning, sincesubtle3 cognitive of changes were noted in patients with CD4a counts less than220/mm . Finally, the incidence of AIDS dementia complex (ADC) in the USAFpopulation was assesed. Clinical ADC affects less than 10% of the USAF AIDS(WR-6) population, significantly less than the 40-70% predicted by others.Possible explanations for this difference may include: 1) USAF study ispopulation based and not referral biased, 2) Cognitive testing was not alwaysaccomplished during the terminal stages of the illness, 3) the average age ofour population is less than 30, and/or 4) other centers reflect experience witha more neurotropic virus. All of the above data concerning cognitive functionin HIV infected individuals was presented at the American Academy of Neurologyin April 1988, and published in Neurology 1989; vol 39 (3) - supplement 1.

In addition, two other neurologically related studies have beenaccomplished. The first concerned the presence of anti-cardiolipin IgGantibodies in the CSF of HIV infected patients. Twelve patients with highserum anti-cardiolipin IgG/IgM and increased total CSF IgG levels were assayedfor CSF anti-cardiolipin antibody IgG/IgM. There was no significantdifference between patients and controls for CSF anti-cardiolipin antibody IgM,but 9 of 12 had abnormal CSF anti-cardiolipin IgG levels. CSF anti-cardiolipinIgG levels should, therefore, be evaluated for potential as a marker fordevelopment of HIV-related CNS disease. And finally, a study of nerveconduction velocities on nearly 300 HIV-infected Individuals, predominantlywith no symptoms of peripheral neuropathy, demonstrated a significantdifference in groups according to CD4a counts. Clearly those with fewer than200 CD4a cells/mm had several nerve conduction parameters which weresignificantly different compared to the higher CD4a cell count groups. Forseveral parameters there was a progressive decline in the nerve conductionparameters associated with decline in CD4a counts. These individuals, however,

2

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rarely had any symptoms of peripheral neuropathy. Thus, Immunological declinemay have associated asymptomatic changes in peripheral nerve which necessitatefurther study.

IV. Oral Hairy Leukoplakia Study

An investigation into the significance of oral hairy leukoplakia (OHL) hasbeen undertaken and to date approximately 85 cases have been identified acrossall Walter Reed stages. Of these 72 are confirmed by biopsy. The prevalenceof biopsy confirmed OHL in our entire cohort is approximately 9%. Whenstatistical analyses were performed on a battery of laboratory andimmunological parameters of OHL-positive vs OHL-negative HIV positiveindividuals, there were no statistically significant differences seen in themean values between these two groups. However, a subgroup of seven individualswho have progressed to AIDS from lower Walter Reed stage disease have beenobserved over a period of 18 months. In this subgroup of individuals, therewere statistically significant higher mean serum IgA levels, lower helper/suppressor ratios and presence of partial or complete anergy (with greater than400 CD4a positive cells) and a more rapid fall in CD4a cell number over time.Although numbers are small it appears that this patient population partiallyconfirms the results of Greenspan et al, (JID 1987:155;475) who report up to80% progression to AIDS over a 30 month period. It is felt that our datashowed that OHL is a significant marker for disease progression but thatpercentages of progression to AIDS from early stage disease may be much lowerthan that reported by Greenspan, et al, because of the overall earlier stage ofour patient population.

3

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Publications During the Past Year that Acknowledge Support of this Contract

1. Reed KD, Fowler CB, Brannon RB. Ultrastructural Detection of Herpes-TypeVirions by Negative Staining in Oral Hairy Leukoplakia. Am J Clin Pathol90(3):305-308, September 1988.

2. Parker W, Hensley K, et al. Heterogeneity of the T4 Epitope (T4) and itsEffect on Classification HIV-Infected Individuals. Published in the New EngJournal of Med as a Letter to the Editor, May 1988.

3. Rundell JR, Beatty DC, Paolucci SL, Boswell RN. Psychiatric Illness atAll Stages of Human Immunodeficiency Virus Infection. Am J Psychiatry145:652-653, May 1988.

4. Alsip GR, Ench Y, Sumaya CV, Boswell RN. Increased Epstein-Barr VirusDNA in Oropharyngeal Secretions from Patients with AIDS, AIDS-Related Complexor Asymptomatic Human Immunodeficiency Virus Infection. J Infectious Diseases157:1072-1076, May 1988.

5. Marshall DW. HIV Penetration of the BBB. Neurology 38:1000-1001, 1988.

6. Marshall DW, Brey RL, Cahill WT, Houk RW, Zajac RA, Boswell RN. Spectrumof CSF Findings in Various Stages of HIV Infection. Arch Neurology 45:954-958, September 1988.

7. Appleman ME, Marshall DW, Brey RL, Houk RW, Beatty DC, Winn KE, MelcherGP, Wise MG, Sumaya CV, Boswell RN. Cerebrospinal Fluid Abnormalities inPatients Without AIDS Who Are Seropositive for the Human ImmunodeficiencyVirus Infections. J Infectious Diseases 158:193-199, July 1988.

8. Boswell RN. AIDS 1988. J Arkansas Med Society 85:73-85, April 1988.

9. Zajac RA, Winn RE. Acquired Immunodeficiency Syndrome. Critical Care,Kirby, Civetti, Taylor, (Eds), Lippincott, 1988.

10. Fling JA, Fischer JR, Boswell RN, Reid MJ. The Relationship of Serum IgAConcentration to HIV Infection: A Cross-Sectional Study of HIV SeropositiveIndividuals Detected by Screening in the USAF. J Allergy & ClinicalImmunology 82:965, December 1988.

11. Berger R, Hobbs E, Stoner M, Hayes T, Boswell R. Cutaneous Manifesta-tions of Early Human Immunodeficiency Exposure. J Academy Derm 19:298-303,1988.

PRESENTATIONS/ABSTRACTS

1. Hensley R. Quality Control of Immunophenotyping. Presented at the SanAntonio Flow Cytometer Users Group Meeting. San Antonio, TX, December 1988.

2. Davis H, Hensley R. Organization and Methodology of Cryopreservation ofHIV+ Specimens for Storage. Presented at the Ist Annual Flow Cytometry Forum,San Antonio, TX, March 1988.

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3. Boswell RN, Zajac R, Dreesman C, Houk R, Paul D, Dawson C, Marshall D,Brey R. HIV Viral Culture, Detection of Viral Antigen and QuantitativeAntibody Levels in Serum and CSF. Presented at the 4th InternationalConference on AIDS, Stockholm, Sweden, June 1988.

4. Hensley R. Flow Cytometry - An Overview at WHMC. Presented at the USAFEpidemiological Laboratory, San Antonio, TX, March 1988.

5. Parker W, Hensley R. Heterogeneity of the T4 Epitope (T4). Presented atthe Ist Annual Flow Cytometry Forum, San Antonio, TX, March 1988

6. Zefo N, Weiland FL, Zajac R. Comparison of In-III Leukocytes and Ga-67Scintigraphy on the Evaluation of the HIV+ Patient. Radiological Society ofNorth American 74th Scientific Assembly and Annual Meeting, 27 Nov-2 Dec,1988.

7. Pavey E, Hensley R. A Normal Range Study of Three Manufacturers'Monoclonal Antibodies for the Enumeration of T-Lymphocytes Using Laser-BasedFlow Cytometry. Presented at the Society of Armed Forces Medical LaboratoryScientists, Reno, NV, March 1988.

8. Hensley R. Flow Cytometry - A Look Into The Cell. Presented at theTexas State Society of the American Medical Technologist Spring StateConvention, March 1988.

9. Parker W, Hensley K. Heterogeneity of the T4 Epitope (T4) and Its EffectOn Classification HIV-Infected Individuals. Presented at the NationalConvention of Allergy and Immunology, 1988.

10. Way D, Davis H, Brown M, Boswell N. Detection of HIV Antigen; Analysisof HIV Antibody Positive Serum and Cerebral Spinal Fluid Paired SpecimensUsing Two Enzyme-Linked Immunosorbent Assay (ELISA) Systems.

11. Valtier S, Brown M, Benton J. Clinical Experience with Two Enzyme-LinkedImmunosorbent Assay (ELISA) Systems For Detection of HIV Antibodies.Presented at the Society of Armed Forces Medical Laboratory Scientists, Reno,NV, March 1988.

12. Brown GR, Paolucci SL, Pace JV, Kyle KM, Drexler KG, McManis SE. FourHour Symposium during 1988 Behavioral Sciences Symposium at Sheppard AFB onHIV Positivity and Psychiatry, November 1988.

13. Brown GR. Psychiatric Issues in HIV Positive Individuals. Texas MedicalAssociation Annual Session, San Antonio, TX, May 1988.

14. Brown GR, Rundell JR. Psychiatric Disorders at All Stages of HIVInfection. Proceedings of the 1988 Annual Session of the Texas MedicalAssociation, May 1988.

15. Zefo N, Weiland PL, Ramos-Gabatin A. Diagnostic Value of Gallium-67Scintigraphy in HIV+ Patients at Wilford Hall USAF Medical Center. Air ForceRegional Meeting of the American College of Physicians 30th Annual Meeting, 28Feb-2 Mar 1988.

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16. Zefo N, Weiland FL, Ramos-Gabatin A. Indium-Ill WBC Leukocytes andGallium-67 Scintigraphy in the HIV+ Patient. Southwestern Chapter Society ofNuclear Medicine, 33rd Annual Meeting, 18-20 March 1988.

17. Zefo N, Weiland FL, Ramos-Gabatin A. Gallium-67 Scintigraphy in theEvaluation of HIV+ Patients. Southwestern Chapter, Society of NuclearMedicine 33rd Annual Meeting, 18-20 March 1988.

18. Zajac RA, Winn RE, Melcher GP, Boswell RN, Friedstrom SR, Piper JP, CarrRW, Mumm A, Wiesenfeld R. HIV Disease in USAF Active Duty and DependentPersonnel. Presented at 30th Annual Air Force Regional Meeting of theAmerican College of Physicians, San Antonio, TX, March 1988.

19. Marshall DW, Goethe KE, Brey RL, Cahill WT. Neurological andNeuropsychological Status of Human Immunodeficiency Virus (HIV) Serum AntibodyPositive Asymptomatic Patients. Society of Air Force Physicians 30th AnnualMeeting, 28 Feb-2 Mar 1988.

20. Zajac R, Abbadessa S, Jaso R, Houk R, Reid M, Melcher G, Winn R, DressmanG, Mumm A, Carr R, Boswell RN. U.S. Air Force HIV Natural History Study.Presented at the 4th International Conference on AIDS, Stockholm, Sweden, June1988.

21. Zajac R, Houk R, Zefo N, Weiland F, Jaso R, Abbadessa S, Fowler C, SykesR, Boswell RN. Sarcoidosis and HIV Infection. Presented at the 4thInternational Conference on AIDS, Stockholm, Sweden, June 1988.

22. Sumaya C, Ench Y, Boswell RN. Epstein-Barr Virus Antibodies Correlatedwith Advancing HIV Infections. Presented at the 4th International Conferenceon AIDS, Stockholm, Sweden, June 1988.

23. Appleman ME, Marshall DW, Brey RL, Houk RW, Beatty DC, Winn RE, BoswellRN. Cerebrospinal Fluid Abnormalities in Patients Seropositive to the HumanImmunodeficiency Virus Without the Acquired Immunodeficiency Syndrome.Presented at 30th Annual Air Force Regional Meeting of the American College ofPhysicians, San Antonio, TX, March 1988.

24. Bell A, Atkins J, Zajac R, Boswell RN. HIV and Sensorineural HearingLoss. Presented at the 4th International Conference on AIDS, Stockholm,Sweden, June 1988.

25. Carr R, Mumm A, Zajac R, Marshall D, Wolfe W, Reid M, Boswell RN.Epidemiology-Progression of HIV Disease by Walter Reed Stage in the USAF.Presented at the 4th International Conference on AIDS, Stockholm, Sweden, June1988.

26. Mumm A, Carr R, Zajac R, Melcher 6, Winn R, Boswell RN. Epidemiology ofU.S. Air Force-Wide Screening for HIV Seropositivity. Presented at the 4thInternational Conference on AIDS, Stockholm, Sweden, June 1988.

27. Zefo N, Weiland F, Zajac R, Abbadessa S, Boswell RN. Utility of Gallium-67 Scanning in HIV+ Patients with Pulmonary Disease. Presented at the 4thInternational Conference on AIDS, Stockholm, Sweden, June 1988.

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28. Rundell J, Thomason J, Zajac R, Beatty D, Boswell RN. PsychiatricDiagnosis and Attempted Suicide in HIV Infected USAF Personnel. Presented atthe 4th International Conference on AIDS, Stockholm, Sweden, June 1988.

29. Vaughn MP, Houk RW, Boswell RN. Identification of an ImmunosuppressiveFactor in HIV Infected Sera. Presented at the 30th Annual Air Force RegionalMeeting of the American College of Physicians, San Antonio, TX, March 1988.

30. Goethe KE, Mitchell J, Marshall D. Neuropsychological Functioning in HIVPatients. 4th International Conference on AIDS, Stockholm, Sweden, June 1988.

31. Cahill WT, Bray RL, Marshall DW. Neurophysiologic and RadiologicEvaluation of Human Immunodeficiency Virus (HIV) Infected Patients. Societyof Air Force Physicians 30th Annual Meeting, 28 Feb-2 Mar 1988.

32. Vaughn M, Chanh T, Dressman C, Hartle E, Houk R, Boswell RN. Inhibitionof Lymphocyte Proliferation by HIV Coat Protein GP120 and Its Association withDisease Progression. Presented at the 44th Annual Meeting American Academy ofAllergy and Immunology, Anaheim, CA, March 1988.

33. Vaughn M, Chanh T, Dressman G, Hartle E, Houk R, Boswell RN. Inhibitionof Lymphocyte Proliferation by HIV Coat Protein GP120 and Its Association withDisease Progression. Presented at the 4th International Conference on AIDS,Stockholm, Sweden, June 1988.

34. Wolfe P, Harden E, Sumaya C, Boswell RN. An EBV Associated LymphoidMalignancy in a Patient with AIDS: Case Report and Quantitation of EBV DNA inPatients B Cells. Presented at 30th Annual Air Force Regional Meeting of theAmerican College of Physicians, San Antonio, TX, March 1988.

35. Jaso RC, Zajac RA, Beck D, Fowler C, Reed KD, Winn RE, Boswell RN. HumanPapillomavirus (HPV) in HIV Positive Individuals: Condylomata Oral HairyLeukoplakia and Cervical Dysplasia. Presented at 30th Annual Force RegionalMeeting of the American College of Physicians, San Antonio, TX, March 1988.

36. Hartle JE, Vaughn M, Boswell RN, Houk RE. Human Immunodeficiency VirusAntibody Positive Sera Suppression of Mitogen Driven Lymphocyte Proliferation.Presented at 30th Annual Force Regional Meeting of the American College ofPhysicians, San Antonio, TX, March 1988.

37. Reid MJ, Goetz DW, Zajac RA, Boswell RN. The Natural History of HumanImmunodeficiency Virus Infection in Screened HIV Positive USAF Personnel: Apreliminary Report. Presented at 30th Annual Force Regional Meeting of theAmerican College of Physicians, San Antonio, TX, March 1988.

38. Reid M, Goetz D, Zajac R, Boswell RN. The Natural History of HumanImmunodeficiency Virus Infection in Screened HIV Positive USAF Personnel: APreliminary Report. Presented at the 4th International Conference on AIDS,Stockholm, Sweden, June 1988.

39. Brey RL, Houk R, Duginski T, Patel PJ, Boswell RN. AnticardiolipinAntibody and HIV Infection. Presented at 3rd Conference on AntiphospholipidAntibodies, Kingston, Jamaica, January 1988.

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40. Brey R, Marshall D, Cahill W, Zajac R, Houk R, Boswell RN. IntervalChange in Clinical and CSF Parameters in HIV+ Patients. Presented at the 4thInternational Conference on AIDS, Stockholm, Sweden, June 1988.

41. Cahill WT, Brey RL, Marshall DW. Neurophysiologic and RadiologicEvaluation of Human Immunodeficiency Virus (HIV) Infected Patients. Neurology38 (3 Supp):337, 1988.

42. Marshall DW, Brey RL, Cahill WT. Comparison of Cerebrospinal Fluid (CSF)Findings in Human Immunodeficiency (HIV) Infected Asymptomatic (AS) Comparedwith ARC/AIDS Patients. Neurology (3 Supp):119, 1988.

43. Marshall DW, Brey RL, Cahill WR, Houk RW, Boswell RN. ImmunologicAbnormalities of Cerebrospinal Fluid in Asymptomatic Human ImmunodeficiencyVirus Infected Individuals. Presented at American Association of Neurology,Cincinnati, OH, March 1988. Neurology 38 (3 Suppl):167, 1988.

44. Marshall D, Brey R, Cahill W, Zajac R, Houk R, Boswell RN. CSF Findingsin Asymptomatic Individuals Infected by HIV. Presented at the 4thInternational Conference on AIDS, Stockholm, Sweden, Jun 1988. Society of AFPhysicians 30th Annual Meeting, 28 Feb-2 Mar 88. Neurology 38 (3 Suppl):167-168, 1988.

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DISTRIBUTION LIST

5 copies Director

Walter Reed Army Institute of ResearchWalter Reed Army Medical CenterATTN: SGRD-UWZ-C

Washington, DC 20307-5100

1 copy CommanderUS Army Medical Research and Development Command

ATTN: SGRD-RMI-SFort Detrick, Frederick, Maryland 21702-5012

2 copies Defense Technical Information Center (DTIC)

ATTN: DTIC-DDASCameron Station

Alexandria, VA 22304-6145

1 copy DeanSchool of Medicine

Uniformed Service Univesity of theHealth Sciences

4301 Jones Bridge RoadBethesda, MD 20814-4799

1 copy CommandantAcademy of Health Sciences, US Army

ATTN: AHS-CDM

Fort Sam Houston, TX 78234-6100

9